Literature summary for 3.4.24.69 extracted from

Agarwal, R.; Schmidt, J.J.; Stafford, R.G.; Swaminathan, S.
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F (2009), Nat. Struct. Mol. Biol., 16, 789-794.

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Application

Application	Comment	Organism
medicine	BoNT/A is very effective in the therapy of a wide range of human syndromes characterized by hyperactivity of peripheral cholinergic nerve terminals	Clostridium botulinum

Crystallization (Commentary)

Crystallization (Comment)	Organism
BoNT/F in complex with inhibitors VAMP 22-58/Gln58D-cysteine and VAMP 27-58/Gln58D-cysteine, X-ray diffraction structure determination and analysis at 2.1 A and 2.17 A resolution, respectively	Clostridium botulinum

Protein Variants

Protein Variants	Comment	Organism
E110A	the mutant shows similar activity to wild-type BoNT/F	Clostridium botulinum
K29A	the BoNT F K29A mutation does not abrogate VAMP cleavability	Clostridium botulinum
R133A	the BoNT/F mutant shows over 95% reduced activity with VAMP substrate compared to the wild-type enzyme	Clostridium botulinum
R133K	the BoNT/F mutant shows over 95% reduced activity with VAMP substrate compared to the wild-type enzyme	Clostridium botulinum
R171K	the exosite 1 variant BoNT F shows about 98% reduction in activity with VAMP compared to the wild-type enzyme	Clostridium botulinum
Y361A	the BoNT/F mutant shows about 18% reduction in activity with VAMP compared to the wild-type enzyme	Clostridium botulinum

Inhibitors

Inhibitors	Comment	Organism	Structure
VAMP 22-58/Gln58D-cysteine	a substrate-based inhibitor, that binds to BoNT F in the canonical direction but is positioned specifically via three major exosites away from the active site	Clostridium botulinum
VAMP 27-58/Gln58D-cysteine	a substrate-based inhibitor, that binds to BoNT F in the canonical direction but is positioned specifically via three major exosites away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid	Clostridium botulinum

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
VAMP + H2O	Clostridium botulinum	i.e. vesicle-associated membrane protein/synaptobrevin	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Clostridium botulinum	P30996	-	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	activities of wild-type and mutant BoNT/Fs	Clostridium botulinum

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
VAMP + H2O	i.e. vesicle-associated membrane protein/synaptobrevin	Clostridium botulinum	?	-	?
VAMP + H2O	i.e. vesicle-associated membrane protein/synaptobrevin, activity with substrate fragments and mechanism of substrate recognition of BoNT F, overview. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis. In exosite 2, BoNT F Arg133 has a dominant role in allowing docking of the V1-SNARE motif, by interacting with the main chain of VAMP Val43, the side chain of VAMP Glu41 and with a water that interacts with other main chain residues of VAMP. The VAMP E41A mutant is 470% cleavage resistant, as compared to the native VAMP	Clostridium botulinum	?	-	?

Synonyms

Synonyms	Comment	Organism
BoNT F	-	Clostridium botulinum
Clostridium botulinum neurotoxin F	-	Clostridium botulinum

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.000001	-	pH not specified in the publication, temperature not specified in the publication	Clostridium botulinum	VAMP 22-58/Gln58D-cysteine
0.0000019	-	pH not specified in the publication, temperature not specified in the publication	Clostridium botulinum	VAMP 27-58/Gln58D-cysteine

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Release 2023.1 (January 2023)